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PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells
Author(s) -
Ibrahim Mohammad Y.,
Nunez Maria I.,
Harun Nusrat,
Lee J. Jack,
ElNaggar Adel K.,
Ferrarotto Renata,
Wistuba Ignacio,
Myers Jeffrey,
Glisson Bonnie S.,
William William N.
Publication year - 2019
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.25350
Subject(s) - pten , tensin , pi3k/akt/mtor pathway , protein kinase b , immune system , cancer research , cancer , kinase , medicine , biology , immunology , signal transduction , microbiology and biotechnology
Background This study investigated the hypothesis that phosphoinositide 3‐kinase (PI3‐kinase) pathway dysregulation in either head and neck cancer cells and/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC). Methods We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3‐kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p‐Akt, mammalian target of rapamycin (mTOR), phosphorylated‐mammalian target of rapamycin (p‐mTOR), survivin, and Ki‐67). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes. Results Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence‐free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 0.23‐0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15‐0.76, P = .01) on univariate and multicovariate models. Conclusions We identified a novel, negative prognostic role of PI3‐kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI‐3 kinase inhibitors for this disease.